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At a glance

It is a benign disease that is characterized by familial idiopathic jaundice presenting with chronic intermittent conjugated hyperbilirubinemia. The clinical features include always abdominal pain, fatigue, jaundice, very dark urine, and hepatomegalia. The jaundice usually fluctuated in intensity as it is aggravated by intercurrent disease. The pathognomonic sign is the presence of a black liver. The prognosis is excellent.

Synonym

Dubin-Johnson-Sprinz Nelson Syndrome; Chronic Idiopathic Jaundice; Conjugated Hyperbilirubinemia Syndrome; Hyperbilirubinemia Type II Syndrome.

Incidence

Occurs in both sexes (although males are affected about 1.5 times more often than females) and in all nationalities and races. The highest prevalence in the general population (1:1300) is found in Iranian Jews. It is also prevalent in the people of Middle Eastern Jewish heritage. In Japan, Dubin-Johnson Syndrome was found to be highly prevalent in an isolated area of consanguinity. The age at onset has been established between infancy (10 weeks) and as late as 56 years of age.

Genetic inheritance

It is transmitted as autosomal recessive trait. There is a reduced penetrance in females. The gene encoding for the human canalicular multispecific organic anion transporter (cMOAT) protein has been mapped to 10q24.

Pathophysiology

The cMOAT protein is involved in the energy-dependent transport of certain bilirubin glucuronides and organic acids (except bile acids) against a concentration gradient across the canalicular membrane of the hepatocyte. The cMOAT protein defect in Dubin-Johnson Syndrome (DJS) leads to decreased hepatobiliary transport and seems to be responsible for the predominantly conjugated hyperbilirubinemia and the intralysosomal accumulation of pigment in hepatocytes.

Diagnosis

In healthy people, the total daily biliary coproporphyrinogen (CPG) excretion (a by-product of the heme synthesis) is about three times higher than urinary CPG excretion, and urinary CPG III concentration is about three times higher than CPG I concentration. In DJS, the total amount of urinary CPG is normal, but CPG isomer I accounts for 80% of total CPG. Hence, the diagnosis is based on increased levels of CPG I in the urine, whereas the CPG III level is below normal. Furthermore, the rise in the sulfobromophthalein sodium test is delayed, and the liver appears macroscopically dark blue or even black. Histologically, the cytoplasm of hepatocytes (especially in zone III) contains big lysosomes packed with a lipochromic pigment, which is responsible for the brown-black color. This pigment has many similarities to melanin but is not melanin. It has been theorized that the pigment may be composed of polymers of epinephrine metabolites. The amount of pigment is variable; for example, it can disappear almost completely during an acute viral hepatitis but then reappear slowly after recovery.

Clinical aspects

Main findings of the disease are hepatomegaly associated with abdominal pain and jaundice. Although cases in neonates have been ...

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